Many idiopathic diseases have been considered candidates for an infectious etiology despite failure of traditional methods to identify causative agents. Traditional approaches to recognizing microorganisms in such diseases are largely based on culture or immunologic methods, and therefore suffer from the need for prior knowledge about the growth requirements or immunology of the organisms being sought. They therefore are necessarily narrow in scope. Thus, negative results obtained by these means cannot easily be interpreted. The method proposed here, and for which preliminary data is presented, is believed largely to overcome these obstacles. It employs advances in molecular biology and knowledge of ribosomal base sequences that have become available in the past 2-3 years and can detect almost all eubacteria (i.e. all known groups of bacteria, mycoplasmas, chlamydiae and rickettsiae of medical significance) in clinical specimens. The equivalent of about 10 organisms can currently be detected. The method employs synthetic oligonucleotides with broad eubacterial homology to amplify microbial DNA extracted from clinical specimens by the polymerase chain reaction (PCR). Detected organisms can be characterized sufficiently well to help distinguish contaminants from true pathogens. Preliminary studies on infected clinical specimens and controls have demonstrated its applicability. Moreover, formalin-fixed, embedded pathology specimens are also expected to be candidates for study in this way, thus providing specimens not easily obtained otherwise. Among the disorders to be studied by this technique are the chronic arthritides, sarcoidosis and Wegener's granulomatosus. In addition, such disorders as the arthritides accompanying AIDS and other known and potential infectious states will be studied by this technique to provide information of clinical and investigative value.